Nuclear stress bodies: Interaction of its components in oncogenic regulation

Abstract

Oncogenesis involves continuous genetic alterations that lead to compromised cellular integrity and immortal cell fate. The cells remain under excessive stress due to endo‐ and exogenous influences. Human Satellite III long noncoding RNA (SatIII lncRNA) is a key regulator of the global cellular stress response, although its function is poorly explained in cancers. The principal regulator of cancer meshwork is tumor protein p53, which if altered may result in chemoresistance. The heat shock factor 1 (HSF1) being a common molecule between the oncogenic control and global cellular stress acts as an oncogene as well as transcribes SatIII upon heat shock. This prompted us to determine the structure of SatIII RNA and establish the association between SatIII‐HSF1‐p53. We determined the most stable structure of SatIII RNA with the least energy of − 115.7 kcal/mol. Also, we observed a possible interaction of p53 with SatIII and HSF1 using support vector machine (SVM) algorithm for predicting RNA‐protein interaction (RPI). Further, we employ the STRING database to understand if p53 is an interacting component of the nuclear stress bodies (nSBs). A precise inference was drawn from molecular docking which confirmed the interaction of SatIII‐HSF1‐p53, where a mutated p53 resulted in an altered DNA‐binding property with the SatIII molecule. This study being first of its kind infers p53 to be a possible integral component of the nSBs, which may regulate cellular stress response during cancer progression in the presence of HSF1 and SatIII. An extended research on the regulations of SatIII and p53 may open new avenues in the field of apoptosis in cancer and the early approach of molecular targeting.

Human satellite III long noncoding RNA imparts survival benefits to cancer cells

“…Our previous in silico study showed a strong SatIII RNA and p53 protein interaction (Figure 7a,b). The SatIII‐interacting residues present on p53 DNA binding domain appeared functionally significant in cellular stress and cancer, which, if altered, may lead to malignant cell fate (Chatterjee et al, 2019). Several research groups also have shown that p53 intrinsically interacts with specific lncRNAs in cancer (Chaudhary & Lal, 2017; Lin et al, 2019).…”

“…(a) Docked complex representing interactions between SatIII and p53 with interacting amino acid residues present on p53 DNA binding domain (yellow) (adapted from Chatterjee et al, 2019). (b) Molecular interaction analysis by PatchDock beta v1.3 shows interaction between mutp53 and SatIII leads to change in amino acid residues present on p53 DNA binding domain (pink) (adapted from Chatterjee et al, 2019). (c) In control condition (unaltered Sat III levels), p53 expression is low in HeLa cells (upper panel).…”

A Gene Encoding an Architectural RNA,hsrω, is a Host Genetic Modifier of Cancer Progression inDrosophila

“…sat III transcripts are also perturbed in a variety of human cancer cell lines and similar to the involvement of hsrω in biogenesis of omega speckles and their aggregation during stress, the sat III transcripts also form nuclear stress bodies and act as a sink for various RNA processing and heat shock factors [18,33]. Indeed, several other studies [20, 62,63]…”